tbuckley/cabot-search huggingface dataset:
EUS-guided drainage of large walled-off pancreatic necroses using plastic versus lumen-apposing metal stents: a single-centre randomised controlled trial
Authors: John Gásdal Karstensen, Srdan Novovic, Erik Feldager Hansen, Annette Bojer Jensen, Henrik Lovendahl Jorgensen, Morten Laksafoss Lauritsen, Mikkel Parsberg Werge, Palle Nordblad Schmidt
Journal: Gut (2022)

Objective In treating pancreatic walled-off necrosis (WON), lumen-apposing metal stents (LAMS) have not proven superior to the traditional double pigtail technique (DPT). Among patients with large WON (&gt;15 cm) and their associated substantial risk of treatment failure, the increased drainage capacity of a novel 20-mm LAMS might improve clinical outcomes. Hence, we conducted a study comparing the DPT and 20-mm LAMS in patients with large WON. Design A single-centre, open-label, randomised, controlled superiority trial using an endoscopic step-up approach in patients with WON exceeding 15 cm in size. The primary endpoint was the number of necrosectomies needed to achieve clinical success (clinical and CT resolution), while the secondary endpoints included technical success, adverse events, length of stay and mortality. Results Twenty-two patients were included in the DPT group and 20 in the LAMS group, with no significant differences in patient characteristics. The median size of WON was 24.1 cm (P25–P75: 19.6–31.1). The technical success rates were 100% for DPT and 95% for LAMS (p=0.48), while clinical success rates were 95.5% and 94.7%, respectively (p=1.0). The mean number of necrosectomies was 2.2 for DPT and 3.2 for LAMS (p=0.42). Five patients (12%) developed procedure-related serious adverse events (DPT=4, LAMS=1, p=0.35). The median length of stay was 43 (P25–P75: 40–67) and 58 days (P25–P75: 40–86) in the DPT and LAMS groups (p=0.71), respectively, with an overall mortality of 4.8%. Conclusions For treating large WON, LAMS are not superior to DPT. The techniques are associated with comparable needs for necrosectomy and hospital stay, and no gross difference in adverse events. Trial registration number NCT04057846 .
New biomarkers of hepatitis B virus (HBV) infection: HBV RNA and HBV core-related antigen, new kids on the block?
Authors: Young-Suk Lim
Journal: Clinical and Molecular Hepatology (2022)

See the Original "Hepatitis B virus pre-genomic RNA and hepatitis B core-related antigen reductions at week 4 predict favourable hepatitis B surface antigen response upon long-term nucleos(t)ide analogue in chronic hepatitis B" on page 146.
A global biological conservation horizon scan of issues for 2023
Authors: William J. Sutherland, Craig Bennett, Peter N.M. Brotherton, Holly M. Butterworth, Mick N. Clout, Isabelle M. Côté, Jason Dinsdale, Nafeesa Esmail, Erica Fleishman, Kevin J. Gaston, James E. Herbert-Read, Alice Hughes, Hermanni Kaartokallio, Xavier Le Roux, Fiona A. Lickorish, Wendy Matcham, Noor Noor, James E. Palardy, James W. Pearce-Higgins, Lloyd S. Peck, Nathalie Pettorelli, Jules Pretty, Richard Scobey, Mark D. Spalding, Femke H. Tonneijck, Nicolas Tubbs, James E.M. Watson, Jonathan E. Wentworth, Jeremy D. Wilson, Ann Thornton
Journal: Trends in Ecology & Evolution (2022)

We present the results of our 14th horizon scan of issues we expect to influence biological conservation in the future. From an initial set of 102 topics, our global panel of 30 scientists and practitioners identified 15 issues we consider most urgent for societies worldwide to address. Issues are novel within biological conservation or represent a substantial positive or negative step change at global or regional scales. Issues such as submerged artificial light fisheries and accelerating upper ocean currents could have profound negative impacts on marine or coastal ecosystems. We also identified potentially positive technological advances, including energy production and storage, improved fertilisation methods, and expansion of biodegradable materials. If effectively managed, these technologies could realise future benefits for biological diversity.
Screening strategy for non-alcoholic fatty liver disease
Authors: Saisai Zhang, Lung-Yi Mak, Man-Fung Yuen, Wai-Kay Seto
Journal: Clinical and Molecular Hepatology (2022)

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, affecting approximately 25% of the general population worldwide, and is forecasted to increase global health burden in the 21st century. With the advancement of non-invasive tests for assessing and monitoring of steatosis and fibrosis, NAFLD screening is now feasible, and is increasingly highlighted in international guidelines related to hepatology, endocrinology, and pediatrics. Identifying high-risk populations (e.g., diabetes mellitus, obesity, metabolic syndrome) based on risk factors and metabolic characteristics for non-invasive screening is crucial and may aid in designing screening strategies to be more precise and effective. Many screening modalities are currently available, from serum-based methods to ultrasonography, transient elastography, and magnetic resonance imaging, although the diagnostic performance, cost, and accessibility of different methods may impact the actual implementation. A two-step assessment with serum-based fibrosis-4 index followed by imaging test vibration-controlled transient elastography can be an option to stratify the risk of liverrelated complications in NAFLD. There is a need for fibrosis surveillance, as well as investigating the cost-effectiveness of different screening algorithms and engaging primary care for first-stage triage screening.
Sustained activation of non-canonical NF-κB signalling drives glycolytic reprogramming in doxorubicin-resistant DLBCL
Authors: Shen Kiat Lim, Chen Chen Peng, Shannon Low, Varsheni Vijay, Andrea Budiman, Beng Hooi Phang, Jing Quan Lim, Anand D. Jeyasekharan, Soon Thye Lim, Choon Kiat Ong, Suet-Mien Tan, Yinghui Li
Journal: Leukemia (2022)
TXNIP Suppresses the Osteochondrogenic Switch of Vascular Smooth Muscle Cells in Atherosclerosis
Authors: Sang-Ho Woo, Dongsoo Kyung, Seung Hyun Lee, Kyu Seong Park, Minkyu Kim, Kibyeong Kim, Hyo-Jung Kwon, Young-Suk Won, Inpyo Choi, Young-Jun Park, Du-Min Go, Jeong-Seop Oh, Won Kee Yoon, Seung Sam Paik, Ji Hyeon Kim, Yong-Hwan Kim, Jae-Hoon Choi, Dae-Yong Kim
Journal: Circulation Research (2022)

The osteochondrogenic switch of vascular smooth muscle cells (VSMCs) is a pivotal cellular process in atherosclerotic calcification. However, the exact molecular mechanism of the osteochondrogenic transition of VSMCs remains to be elucidated. Here, we explore the regulatory role of TXNIP (thioredoxin-interacting protein) in the phenotypical transitioning of VSMCs toward osteochondrogenic cells responsible for atherosclerotic calcification.The atherosclerotic phenotypes of Txnip-/- mice were analyzed in combination with single-cell RNA-sequencing. The atherosclerotic phenotypes of Tagln-Cre; Txnipflox/flox mice (smooth muscle cell-specific Txnip ablation model), and the mice transplanted with the bone marrow of Txnip-/- mice were analyzed. Public single-cell RNA-sequencing dataset (GSE159677) was reanalyzed to define the gene expression of TXNIP in human calcified atherosclerotic plaques. The effect of TXNIP suppression on the osteochondrogenic phenotypic changes in primary aortic VSMCs was analyzed.Atherosclerotic lesions of Txnip-/- mice presented significantly increased calcification and deposition of collagen content. Subsequent single-cell RNA-sequencing analysis identified the modulated VSMC and osteochondrogenic clusters, which were VSMC-derived populations. The osteochondrogenic cluster was markedly expanded in Txnip-/- mice. The pathway analysis of the VSMC-derived cells revealed enrichment of bone- and cartilage-formation-related pathways and bone morphogenetic protein signaling in Txnip-/- mice. Reanalyzing public single-cell RNA-sequencing dataset revealed that TXNIP was downregulated in the modulated VSMC and osteochondrogenic clusters of human calcified atherosclerotic lesions. Tagln-Cre; Txnipflox/flox mice recapitulated the calcification and collagen-rich atherosclerotic phenotypes of Txnip-/- mice, whereas the hematopoietic deficiency of TXNIP did not affect the lesion phenotype. Suppression of TXNIP in cultured VSMCs accelerates osteodifferentiation and upregulates bone morphogenetic protein signaling. Treatment with the bone morphogenetic protein signaling inhibitor K02288 abrogated the effect of TXNIP suppression on osteodifferentiation.Our results suggest that TXNIP is a novel regulator of atherosclerotic calcification by suppressing bone morphogenetic protein signaling to inhibit the transition of VSMCs toward an osteochondrogenic phenotype.
Praliciguat Promotes Ischemic Leg Reperfusion in Leptin Receptor-Deficient Mice
Authors: Ninon Foussard, Paul Rouault, Lauriane Cornuault, Annabel Reynaud, Emmanuel S. Buys, Candice Chapouly, Alain-Pierre Gadeau, Thierry Couffinhal, Kamel Mohammedi, Marie-Ange Renault
Journal: Circulation Research (2022)

Background: Lower-limb peripheral artery disease is one of the major complications of diabetes. Peripheral artery disease is associated with poor limb and cardiovascular prognoses, along with a dramatic decrease in life expectancy. Despite major medical advances in the treatment of diabetes, a substantial therapeutic gap remains in the peripheral artery disease population. Praliciguat is an orally available sGC (soluble guanylate cyclase) stimulator that has been reported both preclinically and in early stage clinical trials to have favorable effects in metabolic and hemodynamic outcomes, suggesting that it may have a potential beneficial effect in peripheral artery disease. Methods: We evaluated the effect of praliciguat on hind limb ischemia recovery in a mouse model of type 2 diabetes. Hind limb ischemia was induced in leptin receptor-deficient (Lepr db/db ) mice by ligation and excision of the left femoral artery. Praliciguat (10 mg/kg/day) was administered in the diet starting 3 days before surgery. Results: Twenty-eight days after surgery, ischemic foot perfusion and function parameters were better in praliciguat-treated mice than in vehicle controls. Improved ischemic foot perfusion was not associated with either improved traditional cardiovascular risk factors (ie, weight, glycemia) or increased angiogenesis. However, treatment with praliciguat significantly increased arteriole diameter, decreased ICAM1 (intercellular adhesion molecule 1) expression, and prevented the accumulation of oxidative proangiogenic and proinflammatory muscle fibers. While investigating the mechanism underlying the beneficial effects of praliciguat therapy, we found that praliciguat significantly downregulated Myh2 and Cxcl12 mRNA expression in cultured myoblasts and that conditioned medium form praliciguat-treated myoblast decreased ICAM1 mRNA expression in endothelial cells. These results suggest that praliciguat therapy may decrease ICAM1 expression in endothelial cells by downregulating Cxcl12 in myocytes. Conclusions: Our results demonstrated that praliciguat promotes blood flow recovery in the ischemic muscle of mice with type 2 diabetes, at least in part by increasing arteriole diameter and by downregulating ICAM1 expression.
David Oliver: England is still waiting for social care solutions
Authors: David Oliver
Journal: BMJ (2022)

In Samuel Beckett's Waiting for Godot, Vladimir says, "Well.What do we do?"-to which Estragon replies, "Don't let's do anything.It's safer."Later, Estragon tells us that "nothing happens.Nobody comes.Nobody goes.It's awful." 1 Waiting for meaningful solutions in social care policy feels very similar, with little hope on the horizon.A quick historical timeline serves to emphasise the despair many of us feel, as keenly as Beckett's protagonists.
Distinct Transcriptomic and Proteomic Profile Specifies Patients Who Have Heart Failure With Potential of Myocardial Recovery on Mechanical Unloading and Circulatory Support
Authors: Stavros G. Drakos, Rachit Badolia, Aman Makaju, Christos P. Kyriakopoulos, Omar Wever-Pinzon, Christopher M. Tracy, Anna Bakhtina, Ryan Bia, Timothy Parnell, Iosif Taleb, Dinesh K.A. Ramadurai, Sutip Navankasattusas, Elizabeth Dranow, Thomas C. Hanff, Eleni Tseliou, Thirupura S. Shankar, Joseph Visker, Rana Hamouche, Elizabeth L. Stauder, William T. Caine, Rami Alharethi, Craig H. Selzman, Sarah Franklin
Journal: Circulation (2022)

Extensive evidence from single-center studies indicates that a subset of patients with chronic advanced heart failure (HF) undergoing left ventricular assist device (LVAD) support show significantly improved heart function and reverse structural remodeling (ie, termed "responders"). Furthermore, we recently published a multicenter prospective study, RESTAGE-HF (Remission from Stage D Heart Failure), demonstrating that LVAD support combined with standard HF medications induced remarkable cardiac structural and functional improvement, leading to high rates of LVAD weaning and excellent long-term outcomes. This intriguing phenomenon provides great translational and clinical promise, although the underlying molecular mechanisms driving this recovery are largely unknown.
Cannabinoid Receptor 2-Centric Molecular Feedback Loop Drives Necroptosis in Diabetic Heart Injuries
Authors: Pan Gao, Mengying Cao, Xueli Jiang, Xiaolin Wang, Guoping Zhang, Xinru Tang, Chunjie Yang, Issei Komuro, Junbo Ge, Liliang Li, Yunzeng Zou
Journal: Circulation (2022)

Background: Diabetic heart dysfunction is a common complication of diabetes. Cell death is a core event that leads to diabetic heart dysfunction. However, the time sequence of cell death pathways and the precise time to intervene of particular cell death type remain largely unknown in the diabetic heart. This study aims to identify the particular cell death type that is responsible for diabetic heart dysfunction and to propose a promising therapeutic strategy by intervening in the cell death pathway. Methods: Type 2 diabetes models were established using db/db leptin receptor–deficient mice and high-fat diet/streptozotocin–induced mice. The type 1 diabetes model was established in streptozotocin-induced mice. Apoptosis and programmed cell necrosis (necroptosis) were detected in diabetic mouse hearts at different ages. G protein–coupled receptor–targeted drug library was searched to identify potential receptors regulating the key cell death pathway. Pharmacological and genetic approaches that modulate the expression of targets were used. Stable cell lines and a homemade phosphorylation antibody were prepared to conduct mechanistic studies. Results: Necroptosis was activated after apoptosis at later stages of diabetes and was functionally responsible for cardiac dysfunction. Cannabinoid receptor 2 (CB2R) was a key regulator of necroptosis. Mechanically, during normal glucose levels, CB2R inhibited S6 kinase–mediated phosphorylation of BACH2 at serine 520, thereby leading to BACH2 translocation to the nucleus, where BACH2 transcriptionally repressed the necroptosis genes Rip1 , Rip3 , and Mlkl . Under hyperglycemic conditions, high glucose induced CB2R internalization in a β-arrestin 2–dependent manner; thereafter, MLKL (mixed lineage kinase domain-like), but not receptor-interacting protein kinase 1 or 3, phosphorylated CB2R at serine 352 and promoted CB2R degradation by ubiquitin modification. Cardiac re-expression of CB2R rescued diabetes-induced cardiomyocyte necroptosis and heart dysfunction, whereas cardiac knockout of Bach2 diminished CB2R-mediated beneficial effects. In human diabetic hearts, both CB2R and BACH2 were negatively associated with diabetes-induced myocardial injuries. Conclusions: CB2R transcriptionally repressed necroptosis through interaction with BACH2; in turn, MLKL formed a negative feedback to phosphorylate CB2R. Our study provides the integrative view of a novel molecular mechanism loop for regulation of necroptosis centered by CB2R, which represents a promising alternative strategy for controlling diabetic heart dysfunction.
A nanoformulation for immunosuppression reversal and broad-spectrum self-amplifying antitumor ferroptosis-immunotherapy
Authors: Qunfang Yang, Tao Liu, Haiping Zheng, Zechen Zhou, Yan Huang, Honglin Jia, Shixiang Fu, Xuan Zhang, Haigang Zhang, Ya Liu, Xiaohong Chen, Wenjun Shan
Journal: Biomaterials (2022)
Impaired Efferocytosis by Synovial Macrophages in Patients With Knee Osteoarthritis
Authors: Luigi Del Sordo, Garth B. Blackler, Holly T. Philpott, Jared Riviere, Lakshman Gunaratnam, Bryan Heit, C. Thomas Appleton
Journal: Arthritis & Rheumatology (2022)

Objective Osteoarthritis (OA) exposes all joint tissues to physiologic stresses, increasing the need to clear apoptotic cells from tissues, including the synovium. We undertook this study to assess the burden of apoptotic cells in synovial tissue in patients with late‐stage knee OA and to investigate whether OA impairs the macrophage‐mediated clearance of apoptotic cells via efferocytosis. Methods Synovial tissue was collected from individuals with healthy knees and patients with late‐stage knee OA during arthroplasty. Synovial apoptotic cell burden was assessed by immunofluorescence for cleaved caspase 3. Efferocytosis of apoptotic Jurkat cells by CD14+ synovial tissue macrophages and peripheral blood–derived macrophages was quantified using immunofluorescence microscopy. Effects of OA on macrophage‐mediated efferocytosis were modeled by stimulating blood‐derived macrophages with synovial fluid collected from individuals with healthy knees and patients with early‐ or late‐stage knee OA. Results Patients with late‐stage knee OA had more apoptotic synovial cells compared to healthy individuals. There was a marked reduction in the fraction of synovial tissue macrophages engaging in efferocytosis and the quantity of material efferocytosed by individual macrophages in OA patients. Blood‐derived macrophages exposed to synovial fluid from patients with knee OA recapitulated the defective efferocytosis, with the greatest effect from patients with early‐stage knee OA and higher disease activity (pain and inflammation). Conclusion Apoptotic cells accumulate in the synovium of patients with late‐stage knee OA. Our results suggest that OA impairs critical homeostatic functions of synovial macrophages, leading to accumulation of apoptotic cells. image
Abstract 5005: Development and Testing of a Risk Prediction Algorithm for Incident Hypertension in Women with Currently Normal Blood Pressure
Authors: Nina P Paynter, Nancy R Cook, Brendan M Everett, Howard D Sesso, Julie E Buring, Paul M Ridker
Journal: Circulation (2008)

Background : We sought to determine whether a hypertension risk prediction model based on patient characteristics and blood biomarkers might improve upon risk prediction based on current blood pressure alone. Methods : A prospective cohort of 14,822 normotensive women were followed over 8 years for the development of hypertension. Among a randomly selected two-thirds sample (“development cohort”; N=9,427), hypertension prediction models were developed using 52 potential predictors and compared to a model based on blood pressure alone. Each prediction model was validated in the remaining one-third sample (“validation cohort”; N=5,395). Results : In the development cohort, the best prediction model for incident hypertension included age, blood pressure, ethnicity, body mass index, total grain intake, apolipoprotein B, lipoprotein(a), and C-reactive protein. While this model was superior to a model based on blood pressure alone. it was only marginally better than a simplified model including age, blood pressure, ethnicity, and body mass index. In the validation cohort, the best model was no longer calibrated. The simplified model, however, demonstrated adequate calibration in the validation cohort (Hosmer-Lemeshow P-value 0.14), with a c-index similar to that of the best model (0.703 vs 0.705), and when compared to the model based on blood pressure alone (Table ), reclassified 1499 participants to hypertension risk categories that were closer to the observed risk in all but one instance. Conclusion : In this prospective cohort of initially normotensive women, a model based on readily available clinical information predicted incident hypertension better than a model based on blood pressure alone and, unlike more complex models using blood biomarkers, remained calibrated in the validation cohort. Reclassification of Predicted 8-Year Hypertension Risk Categories
Covid-19: Protests against lockdowns in China reignite amid crackdown
Authors: Owen Dyer
Journal: BMJ (2022)

The Chinese government has been struggling to quell protests against lockdowns throughout the country that have exposed the growing strain on its "zero covid" policy in the face of increasingly contagious variants.Police in seven Chinese cities flooded the sites of recent demonstrations on the morning of 29 November, and university students were sent home.But by the evening there were renewed reports of unrest, as social media videos showed police and protesters facing off in the large southern city of Guangzhou.
Impact of Hurricanes and Associated Extreme Weather Events on Cardiovascular Health: A Scoping Review
Authors: Arnab K. Ghosh, Michelle R. Demetres, Benjamin P. Geisler, Shakirah N. Ssebyala, Tianyi Yang, Martin F. Shapiro, Soko Setoguchi, David Abramson
Journal: Environmental Health Perspectives (2022)

The frequency and destructiveness of hurricanes and related extreme weather events (e.g., cyclones, severe storms) have been increasing due to climate change. A growing body of evidence suggests that victims of hurricanes have increased incidence of cardiovascular disease (CVD), likely due to increased stressors around time of the hurricane and in their aftermath.
SIEVE: joint inference of single-nucleotide variants and cell phylogeny from single-cell DNA sequencing data
Authors: Senbai Kang, Nico Borgsmüller, Monica Valecha, Jack Kuipers, Joao M. Alves, Sonia Prado-López, Débora Chantada, Niko Beerenwinkel, David Posada, Ewa Szczurek
Journal: Genome biology (2022)

We present SIEVE, a statistical method for the joint inference of somatic variants and cell phylogeny under the finite-sites assumption from single-cell DNA sequencing. SIEVE leverages raw read counts for all nucleotides and corrects the acquisition bias of branch lengths. In our simulations, SIEVE outperforms other methods in phylogenetic reconstruction and variant calling accuracy, especially in the inference of homozygous variants. Applying SIEVE to three datasets, one for triple-negative breast (TNBC), and two for colorectal cancer (CRC), we find that double mutant genotypes are rare in CRC but unexpectedly frequent in the TNBC samples.
Experimental in vitro, ex vivo and in vivo models in prostate cancer research
Authors: Verena Sailer, Gunhild von Amsberg, Stefan Duensing, Jutta Kirfel, Verena Lieb, Eric Metzger, Anne Offermann, Klaus Pantel, Roland Schuele, Helge Taubert, Sven Wach, Sven Perner, Stefan Werner, Achim Aigner
Journal: Nature Reviews Urology (2022)